This project combines theoretical modeling and laboratory measurements for determining the universal physical principles behind the organization and function of different macromolecular systems. The principal area of interest is that of proteins. Osmotic stress measurements at various solution conditions conducted this year have provided strong evidence that self-assembly of collagen molecules requires the formation of special hydrogen-bonded water bridges between opposing polar residues. The most likely sites of these bridges are two large, identical, histidine-containing sequences located near each end of the collagen molecule. Combined Raman and X-ray experiments have demonstrated that dehydration of reconstituted collagen fibers involves significant changes in interstitial water hydrogen-bond network; the changes are consistent with our theoretical model of hydration forces. In order to better understand features of interstitial water that are essential for collagen interaction and self-assembly, we have now begun measurements of forces between collagen triple helices in non-aqueous solvents having different physical and chemical properties. Direct measurements of temperature-dependent forces between hydroxypropylecellulose molecules have shown several new features of temperature-favored biopolymer self-assembly. The most significant theoretical development this year has been the analysis of possible contributions from water hydrogen-bond-density fluctuations to electrostatic interactions between charged groups separated by several water molecules. In agreement with recent computer simulations this theory predicts oscillating electrostatic potentials that are accounted for in standard macroscopic models.